Sterile Compounding Chapter

Sterile compounding is used to prepare

- Injections (IV, IM, SC, intrathecal)

- Eye drops

- Irrigations

- Pulmonary inhalations

Minimum acceptable standards for sterile compounding

USP 797

CSPs

compounded sterile preparations

SVP

Small volume parenteral

LVP

large volume parenteral

IV solutions >100mL

PEC

Primary engineering controls

Sterile hood that provides ISO 5 air for sterile compounding with HEPA filters

Types: LAFW and CAI

LAFW

laminar airflow workbench

type of open-front sterile hood (PEC): air flow in one direction from the HEPA filter (typically from the back of the hood = horizontal laminar airflow)

positive air pressure

SEC

secondary engineering control

room that contains the PEC

ISO 7

has a minimum ACPH

usually called the "buffer room/area"

positive air pressure protects the CSPs from contamination

SCA

Segregated compounding area (SCA) with unclassified air

used when a cleanroom is not an option

can only be used for certain CSPs

must have a visible, defined perimeter around an SCA

cant be located next to food, warehouse, restroom, windows, doors

usually contain an aseptic compounding isolator (ACI) instead of an LAFW because its closed front

Example: designated space that contains an ISO 5 hood, but is not part of a clean room suite, air in the designated space (room air) is not ISO-rated

CAI

Compounding Aseptic Isolator

type of closed-front ISO 5 sterile hood (PEC) that can be located in a buffer room but is usually located in a SCA

"Glovebox"

Positive air pressure

RABS

Restricted Access Barrier System

any closed-front ISO 5 sterile hood (includes CAIs)

"Glovebox"

surfaces of physical space for CSPs

smooth, impervious, and free from cracks + crevices to make them easy to clean + disinfect

usually stainless steel equipment

surfaces like walls, ceilings, counters, floors, etc

ISO (International Standards Organization)

Sets standards for air quality which is determined by the number and size of particles per volume of air.

The lower the count the cleaner the air.

critical areas ISO requirement

Areas that are closest to exposed sterile drugs + containers (inside the sterile hood (PEC))

Must be at least ISO 5

critical areas for equipment are needle, rubber stopper, and syringe plunger = must stay sterile

ISO for buffer area

at least ISO 7

SEC that contains PEC

anteroom definition and ISO requirement

room adjacent to the SEC where hand washing + garbing occurs (connects the rest of the pharmacy to the buffer room (SEC)

Can be ISO 7 OR 8 for non-HD sterile compounding

line of demarcation

visible line running down the center of the anteroom

separates the room into clean and dirty sections (dirty section is the side closer to the rest of the pharmacy and clean side is closer to buffer room)

how must shoe covers be applied in an anteroom

one at a time as stepping over the line of demarcation

have to keep un-garbed shoe on dirty side and garbed shoe on clean side

ACPH

air changes per hour

- # of times air is replaced in room

Minimum ACPH for SEC

>/= 30 ACPH

Air pressure inside PEC and SEC for non-HD compounding

positive pressure - protects CSPs from contamination

cleanroom suite

One or more sterile hoods (ISO 5 PECs) inside an ISO 7 buffer room (SEC) that is entered through an adjacent anteroom

how to achieve ISO 5 air

by using a sterile hood with a HEPA filter

Direct Compounding Area (DCA)

the space in front of the HEPA filter inside of a PEC

The air coming directly out of the HEPA filter inside of a PEC

first air

cleanest air

injection port and needle must be kept in the first air to prevent contamination

don't block airflow with hands or supplies

work at least 6 inches from the front edge

how often must the HEPA filter inside a PEC be recertified

by a specialist every 6 months and anytime a PEC is moved

types of PECs

• Laminar airflow work benches (LAFW)

• Biological safety cabinets (BSC)

• Compounding aseptic isolators (CAI)

• Compounding aseptic containment isolators (CACI)

designated person

responsible for training and oversight of compounding personnel

must ensure proper training and documentation of all compounders and people who oversee compounders

personnel training documentation requirements for CSPs

initial training must be documented (knowledge + competency demonstrated)

continuous training (ongoing) must be documented and must be completed at least every 12 months

aseptic procedures that stuff must be able to demonstrate that they can do prior to independently compounding CSPs

hand hygiene

garbing + gloving

cleaning + disinfecting space and equipment

sterile drug preparation

how to assess adequate aseptic technique in hand hygiene, garbing, and gloving

by passing a garbing competency evaluation (which is completed >/= 3 times and includes visual observation of procedures and the gloved fingertip test)

how to assess adequate aseptic technique in sterile drug preparation

passing the media fill test and surface sampling

how often must the gloved fingertip test and the media-fill test be completed by compounders

initially and then every 6 months (if compounding only category 1 and 2 CSPs)

Gloved fingertip test

collects a gloved sample from each hand of the compounder by rolling fingerpads/thumbs over a tryptic soy agar plate

plates are incubated >/= 7 days

CFUs (spots on plate) indicate contamination on gloves

How to pass a gloved fingertip test?

Initial: 3 consecutive samples, with zero CFUs for both hands

Ongoing: at least one sample from each hand after media fill test, with goal of

Media-fill test

used to determine if a compounder is preparing CSPs in an aseptic manner

they prepare a small IV bag or vial with tryptic soy broth

multiple aseptic manipulations are done and then the product is incubated

turbidity means contamination is present

How to pass the media-fill test

if the liquid stays clear after 14 days

how often should SECs have their temperature and humidity checked?

once daily

temp 20C or 68F or cooler

humidity 60% or less

how often should CSP storage areas (fridge, freezer) have their temperature checked?

at least daily

How often is air sampling performed?

every 6 months

how often is surface sampling performed?

every 30 days for all classified areas and pass through spaces

at the end of every shift before disinfecting for areas touched most frequently (inside PEC, door handles)

air pressure testing

confirms there is the correct differential between two spaces and ensures that the airflow is unidirectional

pressure gauges are installed in cleanroom space and checked (minimally) once daily or with every work shift (preferred)

how to keep PEC surfaces clean?

keep PECs running at all times

what to do if there is a power outage and the PEC shuts off?

compounding must stop

PEC will need to be cleaned + disinfected and then sterile 70% isopropyl alcohol (IPA) applied prior to restarting compounding

how long must the PEC be on before you can start compounding?

at least 30 minutes

how often must sterile 70% IPA be applied to the PEC work surface throughout the day?

every 30 minutes

what to clean the PEC with

cleaned with a detergent, then a disinfectant, and then with sterile 70% IPA with sterile, low-lint wipes

PECs are cleaned from _____ to _______, ________ to __________

top to bottom, back to front - cleanest first dirtiest last

use slightly overlapping, unidirectional strokes rather than circular motions

use a new side of the wipe for the next area cleaned and replace used wipes often

Cleaning a Horizontal Laminar Airflow PEC:

Clean the:

- ceiling of hood from back to front

- back of the hood (grill over the HEPA filter), from top to bottom

- IV bar and hooks

- side walls starting from back to front, wiping up and down in a long sweeping motion

- anything kept in hood

- bottom surface (work area) starting from back to front, with a side to side motion

- do not start compounding until surfaces have dried

how often should the PEC (and equipment inside) be cleaned, disinfected, and sporicidal disinfectant for cleanrooms?

cleaned: daily

disinfected: daily

sporicidal disinfectant: monthly

how often should the pass-through chambers be cleaned, disinfected, and sporicidal disinfectant for cleanrooms?

cleaned: daily

disinfected: daily

sporicidal disinfectant: monthly

how often should the work surfaces outside the PEC be cleaned, disinfected, and sporicidal disinfectant for cleanrooms?

cleaned: daily

disinfected: daily

sporicidal disinfectant: monthly

how often should the floors be cleaned, disinfected, and sporicidal disinfectant for cleanrooms?

cleaned: daily

disinfected: daily

sporicidal disinfectant: monthly

how often should the walls + doors be cleaned, disinfected, and sporicidal disinfectant for cleanrooms?

cleaned: monthly

disinfected: monthly

sporicidal disinfectant: monthly

how often should the ceiling be cleaned, disinfected, and sporicidal disinfectant for cleanrooms?

cleaned: monthly

disinfected: monthly

sporicidal disinfectant: monthly

how often should the storage shelves + bins be cleaned, disinfected, and sporicidal disinfectant for cleanrooms?

cleaned: monthly

disinfected: monthly

sporicidal disinfectant: monthly

how often should the equipment outside the PEC be cleaned, disinfected, and sporicidal disinfectant for cleanrooms?

cleaned: monthly

disinfected: monthly

sporicidal disinfectant: monthly

Garbing for sterile compounding (9 steps)

Dirtiest to cleanest

1. Before entering anteroom remove coats, rings, watches, bracelets, and makeup. Artificial or long nails are not permitted. Makeup sheds.

2. Don head and facial hair covers and face masks, THEN shoe covers while stepping over the line of demarcation.

3. Hand hygiene with soap and warm water, clean under fingernails to remove debris, fingertips up to elbows for at least 30 seconds. (Depending on sink placement this may come after entering SEC. In that case, alcohol based hand rub should be used before donning garb - like chlorhexidine or povidone-iodine).

4. Dry hands and forearms with low-lint disposable wipes or towels

5. Don low-lint gown (snug around wrist and enclosure at neck), disposable preferred

6. Enter the buffer area (SEC)

7. Apply alcohol based hand rub before donning gloves - like chlorhexidine or povidone-iodine and allow to dry

8. Don sterile, powder free gloves

9. Sanitize gloves with sterile 70% IPA routinely during compounding and when they touch nonsterile. Wait for them to dry before compounding.

where is garbing usually done

anteroom

what is the minimum required garb

head cover

facial hair cover

face mask

shoe covers

gown

sterile gloves

all garb must be used when compounding with an isolator (glove box) unless ________

the isolators manufacturer provides written documentation that garb is not required

When the compounding is completed and the compounding personnel leaves the cleanroom, all garb except for the gown goes into the disposal container. If the gown................._____________________

is not visibly soiled, it can be taken off and kept on the clean side of the anteroom in order to be re-worn for the current work shift.

The gown cannot leave the anteroom if it is going to be re-worn. Hand hygiene is repeated, and all other garb is replaced when entering the compounding area.

doffing garb should not occur at same time and place as others

donning garb

When to Re-Garb in Sterile Compounding

Garb should not be worn outside the anteroom. If the anteroom is exited, complete re-garbing is required, including hand hygiene.

If working in a SCA, and the SCA is left for any reason, re-garbing is required.

________ syringes are commonly used for sterile compounding to ____________ drugs and from and into sterile containers

hypodermic (parenteral) syringes

transfer

what size syringe to draw up CSPs

smallest syringe that can hold desired amount

NOT the exact size of the amount needed, just next closest size up

Luer locks make

secure leak-free connections between syringes, needles, catheters, and IV lines

ampules require

use a filter needle or filter straw to remove the glass from the liquid

vials that contain liquids

a volume of drug is drawn up in a syringe, which can then be added to an IV bag

they'll inject a volume of air equal to the volume of drug that is withdrawn to equalize the pressure

vials that contain lyophilized or freeze-dried powder

powder needs to be reconstituted by adding sterile water for injection (SWFI), bacteriostatic WFI, or a diluent supplied by the manufacturer

Ready-to-use medications (RTUs)

-Prefilled syringes or prepared IV bags

-These are not compounded

- Exp date provided by manufacturer and is on packaging

ready to use vial/bag system (Add-Vantage, Minibag Plus)

drug vial and bag supplied together

nurse squeezes drug into bag at bedside for immediate use

not considered compounded

BUD is by the manufacturer

technology in sterile compounding

ACDs

IVWMS

IV robots

Automated Compounding Devices (ACDs)

aseptically transfer ingredients

should be interfaced with the EHR to prevent transcription errors

IV workflow management systems (IVWMS)

automate the preparation, verification, tracking, and documentation of CSPs

automate workflow

require barcode scanning

take pictures of workflow

Setting Up Items In The Sterile Hood (7 steps)

1. only required items

2. everything should be wiped off with 70% IPA prior to being brought into PEC

3. work in PEC must be at least 6 inches from front

4. all items placed in hood side-by-side and not within 6 inches of the back of the hood

5. nothing between sterile objects and the HEPA filter in a horizontal airflow hood

6. equipment individually wrapped must be opened along the seal inside the PEC to avoid shedding

7. remove waste from area as it is created

what is shedding

release of particles when opening things like sterile equipment

when transferring solutions while making CSPs, swab the ______________ and the ___________ with 70% IPA and wait for it to air dry

rubber top of the vial

port on the IV bag

puncture the rubber top of the vial with needle, _____________ and at a 45 degree angle. Then bring the syringe ____________ while the needle penetrates the stopper.

bevel up

straight up (90 degrees)

Then put air into vial

then invert vial with the attached syringe

coring

when a small piece of rubber from the stopper is aspirated into the needle and is put into the solution in the vial

look for small cored pieces floating near top of CSP during the visual inspection

the supervising pharmacist should _____________________ during visual inspection of syringes while making CSPs

verify that the correct volume of product is in the syringe before compounding continues (see the actual volume in the syringe - NOT the syringe pull-back method)

finished CSPs are ________________________

visually inspected immediately after preparation, against a dark background, for particulates, cored pieces, precipitates, and cloudiness. Container should be lightly squeezed to check for leaks.

Terminal sterilization

required for CSPs compounded with any non-sterile ingredients

methods: steam (autoclave), dry heat, and filtration

CSPs that are heat-labile can be sterilized with

filtration using a sterile 0.22 micron filter

bubble-point test

uses pressure to force liquid to bubble out of the filter to test the filter integrity (when using filtration method for terminal sterilization)

endotoxins

pyrogen produced by both gram positive and gram negative bacteria and fungi

from gram-negative: more potent and dangerous

Pyrogens can come from using ______________ washed with _______________

equipment washed with tap water

To avoid pyrogens, glassware and utensils should be rinsed with ______ and depyrogenated using _____.

sterile water

dry-heat (steam) sterilization with an autoclave

USP categorizes CSPs by...

the risk of contamination

determines their risk level category and BUD

Category 1 CSPs Definition and BUD

are typically prepared in an ISO 5 PEC in an unclassified Segregated Compounding Area (SCA) and have shorter BUDs

no sterility testing required

Category 1 CSPs room temp BUD

Category 1 CSPs refrigerated BUD

Category 2 CSPs

are prepared in a cleanroom suite (ISO 5 PEC in an ISO 7 SEC) and have longer BUDs

sterility testing may be required based on the BUD

Category 3 CSPs

have additional requirements that must be met at all times (such as may require sterility testing)

may be assigned a BUD of up to 180 days

Sterile compounding for emergencies

emergency use/immediate use with no aseptic preparation

BUD of 4h since prepared under suboptimal conditions

Category 2 CSPs Room Temp BUD

Category 2 CSPs Refrigerated BUD

Category 2 CSPs Frozen BUD

Category 3 CSPs Room Temp BUD

Category 3 CSPs Refrigerated BUD